NM_001126334.1:c.1205G>A

Variant names:

• chr9-65283173-C-T
• NM_001126334.1:c.1205G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001126334.1(FOXD4L5):​c.1205G>A​(p.Arg402Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 10)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXD4L5 NM_001126334.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

Genes affected

FOXD4L5 (HGNC:18522): (forkhead box D4 like 5) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anatomical structure morphogenesis; cell differentiation; and regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06857368).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001126334.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXD4L5	NM_001126334.1	MANE Select	c.1205G>A	p.Arg402Lys	missense	Exon 1 of 1	NP_001119806.1	Q5VV16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXD4L5	ENST00000377420.1	TSL:6 MANE Select	c.1205G>A	p.Arg402Lys	missense	Exon 1 of 1	ENSP00000366637.1	Q5VV16

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.60e-7 AC: 1 AN: 1163410 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 579076

African (AFR) AF: 0.00 AC: 0 AN: 27580

American (AMR) AF: 0.00 AC: 0 AN: 34274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21824

East Asian (EAS) AF: 0.00 AC: 0 AN: 31756

South Asian (SAS) AF: 0.00 AC: 0 AN: 71238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3542

European-Non Finnish (NFE) AF: 0.00000113 AC: 1 AN: 886608

Other (OTH) AF: 0.00 AC: 0 AN: 49720

GnomAD4 genome Cov.: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.1
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00062	N
LIST_S2	Benign	0.31	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.069	T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.13	T
Polyphen		0.0	B
Vest4		0.086
MutPred		0.26		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.048
ClinPred		0.077	T
GERP RS		-0.38
Varity_R		0.11
gMVP		0.019
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr9-70176779;